Efficacy of Glucagon-like Peptide-1 Receptor Agonists According to Type 2 Diabetes Subtypes

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Efficacy of Glucagon-like Peptide-1 Receptor Agonists According to Type 2 Diabetes Subtypes: an Italian Monocentric Retrospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06120556
• Other study ID #: AOUConsorziale
• Status: Completed
• Start date: June 10, 2023
• Est. completion date: October 31, 2023

Study information

• Verified date: January 2024
• Source: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational retrospective study is to understand whether glucagon-like peptide-1 receptor agonists (GLP-1RA), which are a group of antidiabetes drugs, may act differently in different subtypes of patients with type 2 diabetes.

The main questions it aims to answer are:

• people with type 2 diabetes belonging to specific subtypes respond better (or worse) to GLP-1RA?

• the beneficial effect of GLP-1RA may last longer in people with type 2 diabetes belonging to specific subtypes?

• what are the clinical characteristics that better explain the efficacy and durability of GLP-1 receptor agonists in type 2 diabetes management?

Clinical data from records of patients attending the diabetes outpatient clinic of our facility will be retrieved to compare the outcomes of GLP-1 receptor agonists in patients belonging to four subtypes of type 2 diabetes.

Description:

Patients with type 2 diabetes are all characterized by hyperglycemia, however their probability to develop micro- and micro-vascular complications. A classification of adult-onset diabetes in 5 subtypes was recently proposed: severe autoimmune diabetes (SAID - including type 1 diabetes and latent autoimmune diabetes in adults LADA), severe insulin resistant diabetes (SIRD), severe insulin deficient diabetes (SIDD), mild age related diabetes (MARD), mild obesity-related diabetes (MOD). This classification has been validated in a multiple populations of patients with recent onset diabetes (within 5 years).

However, this classification requires the measurement of c-peptide/insulinemia or anti- glutamic acid decarboxylase (GAD) antibodies, limiting its applicability in everyday clinical practice. An alternative algorithm requiring easily available clinical characteristics, such as BMI, height, waist circumference, HbA1c, fasting blood glucose, lipid profile, age and age at diagnosis was recently introduced and validated.

In this retrospective observational study, the calculated sample size was of 128 patients, in 4 groups, with alpha 0.05, 1-beta 0.80, effect size 0.3.

The following data will be retrieved for eligible patients: age, sex, diabetes duration, age at diagnosis, antidiabetes therapy, body weight, height, waist circumference, fasting blood glucose, HbA1c, total and HDL and LDL cholesterol, triglycerides, creatinine, microalbuminuria. The algorithm available online (https://uiem.shinyapps.io/diabetes_clusters_app/), will be used to assign enrolled patients to the 4 subtypes of type 2 diabetes (SIDD, SIRD, MARD, MOD).

If available, information regarding micro- and macro-vascular complications of diabetes will be retrieved.

All data will be collected at baseline visit and every follow-up visit (the first follow-up visit should 6-12 months following prescription of a GLP-1 receptor agonist).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: October 31, 2023
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Italian patients with type 2 diabetes

• Onset of diabetes at = 50 years

• Diagnosis of type 2 diabetes = 5 years from enrollment

• BMI = 25 kg/m2

• Patients receiving a GLP-1RA prescription for the first time with at least one follow-up visit at 6-12 months from first prescription

Exclusion Criteria:

• Autoimmune diabetes, monogenic diabetes, secondary diabetes

• History of diabetic ketoacidosis

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• GLP-1 receptor agonist
Patients initiating a GLP-1 receptor agonist (i.e. liraglutide, dulaglutide, semaglutide) will be included in the study.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero-Universitaria Policlinico Bari	Bari

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari

Country where clinical trial is conducted

Italy, 

References & Publications (3)

Ahlqvist E, Storm P, Karajamaki A, Martinell M, Dorkhan M, Carlsson A, Vikman P, Prasad RB, Aly DM, Almgren P, Wessman Y, Shaat N, Spegel P, Mulder H, Lindholm E, Melander O, Hansson O, Malmqvist U, Lernmark A, Lahti K, Forsen T, Tuomi T, Rosengren AH, Groop L. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018 May;6(5):361-369. doi: 10.1016/S2213-8587(18)30051-2. Epub 2018 Mar 5. — View Citation

Bello-Chavolla OY, Bahena-Lopez JP, Vargas-Vazquez A, Antonio-Villa NE, Marquez-Salinas A, Fermin-Martinez CA, Rojas R, Mehta R, Cruz-Bautista I, Hernandez-Jimenez S, Garcia-Ulloa AC, Almeda-Valdes P, Aguilar-Salinas CA; Metabolic Syndrome Study Group; Group of Study CAIPaDi. Clinical characterization of data-driven diabetes subgroups in Mexicans using a reproducible machine learning approach. BMJ Open Diabetes Res Care. 2020 Jul;8(1):e001550. doi: 10.1136/bmjdrc-2020-001550. — View Citation

Dennis JM, Shields BM, Henley WE, Jones AG, Hattersley AT. Disease progression and treatment response in data-driven subgroups of type 2 diabetes compared with models based on simple clinical features: an analysis using clinical trial data. Lancet Diabetes Endocrinol. 2019 Jun;7(6):442-451. doi: 10.1016/S2213-8587(19)30087-7. Epub 2019 Apr 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in HbA1c change from baseline (%) among SIDD, SIRD, MARD, MOD subtypes		Difference in HbA1c change from baseline will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Secondary	Difference in time to failure among SIDD, SIRD, MARD, MOD subtypes	In patients reaching HbA1c <7% at first follow-up visit, the difference in time to failure (defined as HbA1c equal or above 7%)	Difference in time to failure will be assessed up to the last available visit (up to 36 months)
Secondary	Difference in fasting blood glucose change from baseline (mg/dl) among SIDD, SIRD, MARD, MOD subtypes	mg/dl	Difference in fasting blood glucose change from baseline (mg/dl) will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Secondary	Difference in body weight change from baseline (kg) among SIDD, SIRD, MARD, MOD subtypes	kg	Difference in body weight change from baseline (kg) will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)
Secondary	Difference in percentage of patients reaching HbA1c below 7% among SIDD, SIRD, MARD, MOD subtypes		Difference in percentage of patients reaching HbA1c below 7% will be evaluated at first follow-up visit (occurring 6-12 months from GLP-1RA initiation)